Mitosis-specific mechanosensing and contractile-protein redistribution control cell shape
Mitosis-specific mechanosensing and contractile-protein redistribution control cell shape
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DOI：
10.1016/j.cub.2006.08.027
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发表时间：
2006-10-10
期刊：
影响因子：
9.2
通讯作者：
Robinson, Douglas N.
中科院分区：
文献类型：
--
作者：
Effler, Janet C.;Kee, Yee-Seir;Robinson, Douglas N.
因为细胞分裂失败是有害的，会促进哺乳动物的肿瘤发生[1]，细胞利用多种机制来控制它们的细胞周期进程[2-4]。虽然细胞分裂被认为是一系列有序的生化事件[5]，但细胞质分裂是一个内在的机械过程，也必须受到机械控制，以确保产生两个相同的子细胞以高保真。考虑到细胞对机械环境的反应[6，7]，我们假设细胞在胞质分裂过程中利用机械传感和机械反馈来感知和纠正形状不对称。由于有丝分裂纺锤体和肌球蛋白II对细胞分裂至关重要[8，9]，我们探索了它们在细胞分裂过程中响应形状扰动的作用。我们证明了收缩蛋白肌球蛋白II和皮质素I响应于内在和外部诱导的形状不对称而重新分布。在早期的胞质分裂中，机械负荷覆盖纺锤体线索，减缓胞质分裂进程，而收缩蛋白积累并纠正形状不对称。在胞质分裂晚期，机械扰动也会引导收缩蛋白，但不会明显干扰胞质分裂。值得注意的是，这种反应只发生在细胞胞质分裂的后期，不需要微管，不依赖于纺锤体的取向，而是依赖于肌球蛋白II。我们的数据为有丝分裂期间指导收缩蛋白调节细胞形状的机械感觉系统提供了证据。
Because cell-division failure is deleterious, promoting tumorigenesis in mammals [1], cells utilize numerous mechanisms to control their cell-cycle progression [2-4]. Though cell division is considered a well-ordered sequence of biochemical events [5], cytokinesis, an inherently mechanical process, must also be mechanically controlled to ensure that two equivalent daughter cells are produced with high fidelity. Given that cells respond to their mechanical environment [6,7], we hypothesized that cells utilize mechanosensing and mechanical feedback to sense and correct shape asymmetries during cytokinesis. Because the mitotic spindle and myosin II are vital to cell division [8, 9], we explored their roles in responding to shape perturbations during cell division. We demonstrate that the contractile proteins myosin II and cortexillin I redistribute in response to intrinsic and externally induced shape asymmetries. In early cytokinesis, mechanical load overrides spindle cues and slows cytokinesis progression while contractile proteins accumulate and correct shape asymmetries. In late cytokinesis, mechanical perturbation also directs contractile proteins but without apparently disrupting cytokinesis. Significantly, this response only occurs during anaphase through cytokinesis, does not require microtubules, and is independent of spindle orientation, but is dependent on myosin II. Our data provide evidence for a mechanosensory system that directs contractile proteins to regulate cell shape during mitosis.